The prion protein, PrP for short, is found throughout the body of humans and other animals. PrP exists in two forms. The normal endogenous form of PrP, called PrPC or cellular PrP, is non-infectious. In contrast, the second form of PrP, called PrPSC, is infectious. The difference is primarily attributable to the fact that the molecular structure of PrPSC is mis-folded relative to that of PrPC.
PrPSC is responsible for causing prion diseases, including transmissible spongiform encephalopathies such as mad cow disease and Creutzfeldt-Jakob disease. PrPSC is also responsible for generating amyloid fibrils in neural tissue, which can result in irreversible neurodegeneration.
PrPC, on the other hand, appears to be involved in numerous cellular functions, including signal transduction, neuroprotection, and angiogenesis.
Heme is an iron containing component of hemoproteins such as hemoglobin and is an essential component of oxygen transport. Hemin, a derivative of heme, is produced by the body and is released in a vascular injury event such as a stroke.
Hemin toxicity is a source of brain damage following hemorrhagic stroke. Hemorrhagic stroke involves the rupture of an intracerebral artery, which subsequently results in a hematoma caused by the pooling of blood. This prevents the cells from receiving oxygen and vital nutrients, causing the cells to die. After the acute brain injury caused by the stroke, brain damage can continue to occur over the following days and weeks. This has been attributed to the presence of hemin at the site of the hematoma (Robinson, et al, “Hemin toxicity: a preventable source of brain damage following hemorrhagic stroke.” Redox Report, Vol. 14, No. 6 (2009)). According to Robinson, et al., elevated levels of hemin can be toxic, causing tissue injury and even death. Blood contains about 2.5 mM of hemoglobin, which, when broken down can yield 10 mM of hemin. Cell culture experiments suggest that as little as 3-30 μM of hemin is sufficient to kill 60%-70% of cultured neurons and astrocytes within 4-14 hours.